Type I Interferon Signaling Controls Gammaherpesvirus Latency In Vivo

Gammaherpesviruses, such as Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus, are important human pathogens involved in lymphoproliferative disorders and tumorigenesis. Herpesvirus infections are characterized by a biphasic cycle comprised of an acute phase with lytic replication and a...

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Bibliographic Details
Published in:Pathogens 2022, Vol.11 (12)
Main Authors: Schwerk, Johannes, Kemper, Lucas, Bussey, Kendra A, Lienenklaus, Stefan, Weiss, Siegfried, Čičin-Šain, Luka, Kröger, Andrea, Kalinke, Ulrich, Collins, Christopher M, Speck, Samuel H, Messerle, Ma, Wirth, Dagmar, Brinkmann, Melanie M, Hauser, Hansjörg, Köster, Mario
Format: Report
Language:English
Subjects:
Diagnosis
Genetic aspects
Health aspects
Herpes
Herpesvirus diseases
Interferon
Online Access:Get full text
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Summary:Gammaherpesviruses, such as Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus, are important human pathogens involved in lymphoproliferative disorders and tumorigenesis. Herpesvirus infections are characterized by a biphasic cycle comprised of an acute phase with lytic replication and a latent state. Murine gammaherpesvirus 68 (MHV-68) is a well-established model for the study of lytic and latent life cycles in the mouse. We investigated the interplay between the type I interferon (IFN)-mediated innate immune response and MHV-68 latency using sensitive bioluminescent reporter mice. Adoptive transfer of latently infected splenocytes into type I IFN receptor-deficient mice led to a loss of latency control. This was revealed by robust viral propagation and dissemination of MHV-68, which coincided with type I IFN reporter induction. Despite MHV-68 latency control by IFN, the continuous low-level cell-to-cell transmission of MHV-68 was detected in the presence of IFN signaling, indicating that IFN cannot fully prevent viral dissemination during latency. Moreover, impaired type I IFN signaling in latently infected splenocytes increased the risk of virus reactivation, demonstrating that IFN directly controls MHV-68 latency in infected cells. Overall, our data show that locally constrained type I IFN responses control the cellular reservoir of latency, as well as the distribution of latent infection to potential new target cells.
ISSN:2076-0817
2076-0817
DOI:10.3390/pathogens11121554